The liver represents the single largest repository of antimicrobial activity in the body. The antimicrobial functions of this organ are multifaceted and represent in reality simultaneous cooperation of multiple cell and humoral factors. The difficulties in critically distinguishing these factors experimentally in vivo led us to evaluate liver perfusion techniques as a methodological approach. Our early studies led us to conclude that trapping of bacteria by the liver occurs equally well in the presence and absence of humoral factors but for bactericidal activities to be expressed, humoral factors must be present. The present study outlines experiments which extend this early observation. Using livers from normal animals and animals treated with either silica to decrease phagocytic function or Corynebacterium parvum to activate macrophage populations, we have established that the perfusion model allows us to manipulate the organ in ways which yield data similar to in vivo effects but still allow much greater experimental flexibility. Specific objectives which we will explore include the effects of oxygenation, temperature, and ionic environments on antimicrobial function. Additionally the relative role of phagocytic and fenestrated epithelial tissues in removal (trapping) of organisms in the presence and absence of humoral factors will be explored. Plasma will be fractionated in attempts to learn more of the relative role of complement, antibody, and non-specific humoral opsonins in liver antimicrobial function. Salmonella typhimurium and Candida albicans will be compared as representatives of two common opportunistic pathogens of medical importance. Cumulatively, the data should yield considerably more insight than is presently available on the multifactorial systems which interact resulting in antimicrobial functions of the liver.